A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.     

Are Anti-Beta2-Glycoprotein-I Antibodies Markers for Recurrent Pregnancy Loss in Lupus Anticoagulant/Anticardiolipin Seronegative Women?

Problem  Anti-beta₂-Glicoprotein-1 antibodies (anti-β₂GPI-ab) have been related to recurrent miscarriage (RM) with conflicting results. The aim was to evaluate the role of anti-β₂-GPI-ab as unique biological marker in RM related to antiphospholipid (aPL).
Method of study  A cohort study that included 59 cases, divided in two groups, was designed: group 1 comprised 43 pregnant women with 'obstetric' antiphospholipid syndrome (APS) and group 2 included 16 cases with similar complaints but only having repeatedly anti-β₂-GPI-ab. Previous thrombosis and/or inherited thrombophilia were excluded. Lupus anticoagulant, anticardiolipin antibodies (aCA), anti-β₂-GPI-ab, and other autoantibodies were analyzed. Miscarriages, premature births, pre-eclampsia, live births, placental and systemic thromboses were studied.
Results  No differences in previous obstetric complications were detected ( P  =   1.00–0.164). After the treatment, differences in number of obstetric complications were not seen ( P  =   1.00). Live births were similar in two groups (88.4% and 93.7%; P  =   1.00). Placental thrombosis was equal in both groups, 93.3% versus 80% ( P  =   1.00).
Conclusion  These results suggest that anti-β₂-GPI-ab may be considered a biological marker for obstetric APS.     

Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m²) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.     

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.     

Resumen ejecutivo del Documento de Consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y de la Asociación Española de Cirujanos (AEC) en profilaxis antibiótica en cirugía

Antibiotic prophylaxis in surgery is one of the most effective measures for preventing surgical site infection, although its use is frequently inadequate and may even increase the risk of infection, toxicities and antimicrobial resistance. As a result of advances in surgical techniques and the emergence of multidrug-resistant organisms, the current guidelines for prophylaxis need to be revised.The Sociedad Española de Enfermedades Infecciosas (Spanish Society of Infectious Diseases and Clinical Microbiology) (SEIMC) together with the Asociación Española de Cirujanos (Spanish Association of Surgeons) (AEC) have revised and updated the recommendations for antibiotic prophylaxis in surgery to adapt them to any type of surgical intervention and to current epidemiology. This document gathers together the recommendations on antimicrobial prophylaxis in the various procedures, with doses, duration, prophylaxis in special patient groups, and in epidemiological settings of multidrug resistance to facilitate standardized management and the safe, effective and rational use of antibiotics in elective surgery.     

The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component–clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P = 3.2 × 10⁻⁸; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10⁻²⁰; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10⁻¹⁴; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10⁻¹²; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10⁻¹¹; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10⁻⁹; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10⁻⁸; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10⁻⁸; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes.     

A comparative study of portal vein embolization versus radiation lobectomy with Yttrium-90 micropheres in preparation for liver resection for initially unresectable hepatocellular carcinoma

BackgroundPortal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data.MethodsWe retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease.ResultsSeventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90.ConclusionBoth preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery.     

IMXQB-80: A Quillaja brasiliensis saponin-based nanoadjuvant enhances Zika virus specific immune responses in mice

Vaccine adjuvants are compounds that enhance/prolong the immune response to a co-administered antigen. Saponins have been widely used as adjuvants for many years in several vaccines – especially for intracellular pathogens – including the recent and somewhat revolutionary malaria and shingles vaccines. In view of the immunoadjuvant potential of Q. brasiliensis saponins, the present study aimed to characterize the QB-80 saponin-rich fraction and a nanoadjuvant prepared with QB-80 and lipids (IMXQB-80). In addition, the performance of such adjuvants was examined in experimental inactivated vaccines against Zika virus (ZIKV). Analysis of QB-80 by DI-ESI-ToF by negative ion electrospray revealed over 29 saponins that could be assigned to known structures existing in their congener Q. saponaria, including the well-studied QS-21 and QS-7. The QB-80 saponins were a micrOTOF able to self-assembly with lipids in ISCOM-like nanoparticles with diameters of approximately 43 nm, here named IMXQB-80. Toxicity assays revealed that QB-80 saponins did present some haemolytical and cytotoxic potentials; however, these were abrogated in IMXQB-80 nanoparticles. Regarding the adjuvant activity, QB-80 and IMXQB-80 significantly enhanced serum levels of anti-Zika virus IgG and subtypes (IgG1, IgG2b, IgG2c) as well as neutralized antibodies when compared to an unadjuvanted vaccine. Furthermore, the nanoadjuvant IMXQB-80 was as effective as QB-80 in stimulating immune responses, yet requiring fourfold less saponins to induce the equivalent stimuli, and with less toxicity. These findings reveal that the saponin fraction QB-80, and particularly the IMXQB-80 nanoadjuvant, are safe and capable of potentializing immune responses when used as adjuvants in experimental ZIKV vaccines.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.